title: The roles of miR-146a in the differentiation of Jurkat T-lymphoblasts.
abstract: BACKGROUND
  T-cell acute lymphoblastic leukemia (T-ALL) is caused by a defect in T-cell maturation to the mature T cell. T-ALL is a poor prognostic hematopoietic malignancy. In order to establish a successful therapeutic treatment plan, it is essential to understand the biology of T-cell development and molecules that contribute to this process. This study uses Jurkat T cells, as a well-established model for in vitro study of T-ALL to investigate the role of the microRNA (miRNA), miR-146a, on gene expressions involved in T-cell differentiation.
  
  
  METHODS
  The permanent over-expression of miR-146a was established using a lentivector that expressed GFP hsa-mir-146a miRNA. We used quantitative real-time polymerase chain reaction and flow cytometry for T-cell differentiation to monitor induction of the differentiation process by assessing changes in expression of some distinct transcription factors and cell surface markers.
  
  
  RESULTS
  Ectopic expression of miR-146a resulted in significant up-regulation of PU.1, c-Fos, CCAAT/enhancer-binding protein alpha (C/EBPα) and GATA3, and slight up-regulation of Foxp3 and Runx1. There was a significant, moderate down-regulation in the expressions of Notch1, LIM-domain only (Lmo2), son of sevenless 1 (SOS1), Ikaros, and signal transducer and activator of transcription 3 (STAT3).
  
  
  CONCLUSIONS
  Our results indicated that ectopic expression of miR-146a could not independently induce differentiation in lymphoblastic cells. However, the expression of multiple genes involved in T-cell differentiation and T-cell CD markers were found to be affected. These results have suggested a potential tumor suppressive, immunomodulatory and cell activator role for miR146-a.
authors.forename: Najmaldin
authors.initials: N
authors.lastname: Saki
authors.forename: Saeid
authors.initials: S
authors.lastname: Abroun
authors.forename: Masoud
authors.initials: M
authors.lastname: Soleimani
authors.forename: Yousef
authors.initials: Y
authors.lastname: Mortazavi
authors.forename: Saeid
authors.initials: S
authors.lastname: Kaviani
authors.forename: Ehsan
authors.initials: E
authors.lastname: Arefian
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D019169:Jurkat Cells; D015458:Leukemia, T-Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D008856:Microscopy, Fluorescence; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D014157:Transcription Factors; D049452:Green Fluorescent Proteins
keywords: Jurkat; T cell; differentiation; miR-146a